The prostaglandins (PGs), a group of natural products occurring in animal tissues, have attracted widespread attention over the past thirty years because of their diverse pharmacological properties and potential clinical applications in a number of therapeutic areas. Samuelsson, B. Angew. Chem. Int. Ed. Engl. 1983, 22, 805; Vane, J. R. Angew. Chem. Int. Ed. Engl. 1983, 22, 741; Bergstorm, S. Angew. Chem. Int. Ed. Engl. 1993, 22, 858 and Nelson, N. A.; Kelly, R. C.; Jhonson, R. A. Chem. Eng. News 1982, 33(60), 30 are referrend to herein for reference. Since the elucidation of their structures in the early 1960s, tremendous efforts have been made for the realization of an efficient chemical synthesis. This is because a sufficient supply of such is very rare, and naturally occurring local hormones rely solely on their total synthesis. Roberts, S. M.; Scheinmann, F. New Synthetic Routes to Prostaglandins and Thromboxanes, Academic Press: New York, 1982; Newton, R. F.; Roberts, S. M. Tetrahedron 1980, 36, 2163; Nicolaou, K. C.; Gasic, G. P.; Barnette, W. E. Angew. Chem. Int. Ed. Engl. 1978, 17, 293; Bindra, J. S.; Bindra, R. Prostaglandin Synthesis, Academic Press: New York, 1977 and Mitra, A. Synthesis of prostaglandins, Wiley-Interscience: New York, 1977 are referred to herein for reference.
For the time being, the potentially most direct and flexible route to prostaglandins is the three component coupling approach. The approach relates to reacting optically active 4-oxygenated 2-cyclopentenone derivatives 3 with organocopper reagents having .omega.-chain (R.omega.Cu) to obtain the enolate 4. Then, the PGs are obtained by the alkylation of the enolate 4 with alkyl halides having .alpha.-chain (R.alpha.-X) (see Scheme 1, Path A). The references concerning the three component coupling approach include Gooding, O. W.; Beard, C. C.; Cooper, G. F.; Jackson, D. Y. J. Org. Chem. 1993, 58, 3681-3686; Gooding, O. W. J. Org. Chem. 1990, 55, 4209-4211 and Suzuki, M.; Yanagisawa, A.; Noyori, R. J. Am. Chem. Soc. 1988, 110, 4718-4726. Exploitation of this three component coupling methodology has, however, been impeded by the inability to directly alkylate the enolate 4 with the alkyl halides having .alpha.-chain (R.alpha.-X). Thus, the desired product, prostaglandins cannot be obtained because of the by-reaction (see Scheme 1, Path B). ##STR2##
Suzuki, M.; Yanagisawa, A.; Noyori, R. J. Am. Chem. Soc. 1985, 107, 3348 and Morita, Y.; Suzuki, M.; Noyori, R. J. Org. Chem. 1989, 54, 1785 have successfully overcome the abovementioned problem by employing copper to tin transmetallation at the enolate 4 stage affording a less basic stannyl enolate which retained its reactivity toward .alpha.-chain alkyl iodide (R.alpha.-X).
Accordingly, it is a prerequiste for further synthetic application of prostaglandins to further silylate the prepared optically active allylic alcohol derivatives to the compound 5 and provide a direct and effective organocopper reagents having .omega.-chain (R.omega.Cu) (see Scheme 2). Noyori, R.; Suzuki, M. Angew. Chem. Int. Ed. Engl. 1984, 23, 847-876; Caton, M. P. L. Tetrahedron 1979, 35, 2705-2742 and Taylor, R. J. K. Synthesis 1985, 364-392 are referred to herein for reference. ##STR3##